Saint Francis University

About: Saint Francis University is a education organization based out in Loretto, Pennsylvania, United States. It is known for research contribution in the topics: Population & Osteoblast. The organization has 1694 authors who have published 2038 publications receiving 87149 citations.

Nephroblastoma overexpressed (Nov) inactivation sensitizes osteoblasts to bone morphogenetic protein-2, but nov is dispensable for skeletal homeostasis.

Abstract: Overexpression of nephroblastoma overexpressed (Nov), a member of the Cyr 61, connective tissue growth factor, Nov family of proteins, inhibits osteoblastogenesis and causes osteopenia. The consequences of Nov inactivation on osteoblastogenesis and the postnatal skeleton are not known. To study the function of Nov, we inactivated Nov by homologous recombination. Nov null mice were maintained in a C57BL/6 genetic background after the removal of the neomycin selection cassette and compared with wild-type controls of identical genetic composition. Nov null mice were identified by genotyping and absent Nov mRNA in calvarial extracts and osteoblast cultures. Nov null mice did not exhibit developmental skeletal abnormalities or postnatal changes in weight, femoral length, body fat, or bone mineral density and appeared normal. Bone volume and trabecular number were decreased only in 1-month-old female mice. In older mice, after 7 months of age, osteoblast surface and bone formation were increased in females, and osteoclast and eroded surfaces were increased in male Nov null mice. Calvarial osteoblasts from Nov null mice displayed enhanced alkaline phosphatase activity, alkaline phosphatase mRNA, and transactivation of a bone morphogenetic protein (BMP)/phosphorylated mothers against decapentaplegic reporter construct in response to BMP-2. Similar results were obtained after the down-regulation of Nov by RNA interference in ST-2 stromal and MC3T3 cells. Osteoclast number was increased in marrow stromal cell cultures from Nov null mice. Surface plasmon resonance demonstrated direct interactions between Nov and BMP-2. In conclusion, Nov sensitizes osteoblasts to BMP-2, but Nov is dispensable for the maintenance of bone mass.

Conditional inactivation of noggin in the postnatal skeleton causes osteopenia.

Abstract: Noggin is an antagonist of bone morphogenetic proteins (BMP), and its overexpression causes suppressed osteoblastogenesis and osteopenia. Global inactivation of Noggin results in severe developmental defects and prenatal lethality, but the consequences of the conditional inactivation of Noggin on the postnatal skeleton are not known. To study the function of noggin in osteoblasts, we generated tissue-specific null Noggin mice by mating Noggin conditional mice, where the Noggin allele is flanked by loxP sequences, with mice expressing the Cre recombinase under the control of the osteocalcin promoter (Oc-Cre). Noggin conditional null mice exhibited decreased weight, shortened femoral length, and generalized osteopenia. Bone histomorphometric and microarchitectural analyses of distal femurs revealed decreased bone volume due to a reduced number of trabeculae in 1- and 3-month-old Noggin conditional null mice. Vertebral microarchitecture confirmed the osteopenia observed in Noggin conditional null mice. Osteoclast number was increased in 1-month-old male Noggin conditional null mice, and bone formation was increased in 3-month-old mice, but female mice did not exhibit increased bone remodeling. In conclusion, Noggin inactivation causes osteopenia, suggesting that BMP in excess have a detrimental effect on bone or that noggin has a BMP-independent role in skeletal homeostasis.

Midsystolic Clicks in Arteriosclerotic Heart Disease

Abstract: Midsystolic clicks (MSC), or nonejection systolic clicks, were discovered in 15 patients with arteriosclerotic heart disease (ASHD). The diagnosis of ASHD was established by the presence of angina or the history of a documented myocardial infarction (MI) or both. The MSCs were recorded in 13 patients. A late systolic murmur was introduced by the MSC in four patients, and one patient had a soft holosystolic murmur. The mitral origin of the MSCs and murmurs was established by noting their change in timing and intensity following administration of vasoactive drugs. One patient underwent cardiac catheterization, and evidence of an old MI and papillary muscle dysfunction (PMD) was demonstrated. We think that the PMD that occurs secondary to ischemic fibrosis in ASHD permits slack chordae tendineae suddenly to become taut in midsystole and produce a snap. Although the mechanism for the production of chordal snaps has been previously postulated, ASHD has only recently been found responsible for producing these s...